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Acetate-induced adenosine mediated effects of ethanol
F J Carmichael1, H Orrego, Y Israel
1Department of Pharmacology, University of Toronto, Ontario, Canada.
Alcohol and Alcoholism (Oxford, Oxfordshire). Supplement
|January 1, 1993
Summary
Ethanol increases hepatic blood flow via acetate, which activates adenosine receptors. Acetate also influences ethanol
Area of Science:
- Pharmacology
- Gastroenterology
- Neuroscience
Background:
- Ethanol administration increases hepatic blood flow, primarily due to enhanced mesenteric blood flow.
- Acetate, a metabolite of ethanol, has been implicated in mediating this circulatory effect.
- Adenosine receptor activation is a proposed mechanism linking acetate metabolism to physiological effects.
Purpose of the Study:
- To investigate the role of acetate in mediating ethanol-induced increases in portal blood flow.
- To determine the involvement of adenosine receptors in the effects of ethanol and acetate on blood flow and central nervous system (CNS) depression.
- To examine the potentiation or antagonism of ethanol's CNS effects by acetate.
Main Methods:
- Administering ethanol and measuring hepatic and mesenteric blood flow.
- Infusing acetate to mimic ethanol-induced blood concentrations and observing its effects on blood flow.
- Utilizing the adenosine receptor blocker 8-phenyltheophylline (8PT) to assess receptor involvement.
- Evaluating the effects of ethanol and acetate on CNS depressant behaviors in animal models.
Main Results:
- Acetate infusion replicated the ethanol-induced increase in portal blood flow.
- 8-phenyltheophylline (8PT) completely blocked the blood flow increases caused by both ethanol and acetate.
- Adenosine receptor activation significantly contributed to ethanol's CNS depressant effects at lower concentrations.
- Acetate potentiated the CNS depressant effects of general anesthetics and showed both potentiation and antagonism of ethanol's behavioral effects.
Conclusions:
- Ethanol-induced increases in hepatic blood flow are mediated by acetate through adenosine receptor activation.
- Adenosine receptor activation plays a crucial role in the central nervous system depressant effects of ethanol, particularly at lower doses.
- Acetate modulates the central nervous system effects of ethanol and general anesthetics via adenosine receptor pathways.